SIRT7 is a NAD+‐dependent deacetylase that controls important aspects of metabolism, cancer, and bone formation. However, the molecular targets and functions of SIRT7 in the kidney are currently ...unknown. In silico analysis of kidney transcripts of the BXD murine genetic reference population revealed a positive correlation between Sirt7 and Slc12a7 mRNA expression, suggesting a link between the corresponding proteins that these transcripts encode, SIRT7, and the K‐Cl cotransporter KCC4, respectively. Here, we find that protein levels and activity of heterologously expressed KCC4 are significantly modulated depending on its acetylation status in Xenopus laevis oocytes. Moreover, SIRT7 interacts with KCC4 in a NAD+‐dependent manner and increases its stability and activity in HEK293 cells. Interestingly, metabolic acidosis increases SIRT7 expression in kidney, as occurs with KCC4. In contrast, total SIRT7‐deficient mice present lower KCC4 expression and an exacerbated metabolic acidosis than wild‐type mice during an ammonium chloride challenge. Altogether, our data suggest that SIRT7 interacts with, stabilizes and modulates KCC4 activity through deacetylation, and reveals a novel role for SIRT7 in renal physiology.
SYNOPSIS
The molecular targets and functions of SIRT7 in the kidney are currently unknown. This study demonstrates that SIRT7 interacts with, stabilizes and modulates KCC4 activity through deacetylation, and reveals a novel role for SIRT7 in renal physiology.
KCC4 protein levels and activity are modulated depending on its acetylation status.
SIRT7 interacts with KCC4 and increases its stability and activity through deacetylation.
Metabolic acidosis increased renal SIRT7 expression, while SIRT7‐deficient mice presented lower renal KCC4 expression.
SIRT7 interacts with, stabilizes and modulates KCC4 activity through deacetylation, revealing a novel role for SIRT7 in renal physiology.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
12.
Evidence for the decay Σ+ → pμ+μ PARK, H. K; BURNSTEIN, R. A; GIDAL, G ...
Physical review letters,
01/2005, Volume:
94, Issue:
2
Journal Article
Peer reviewed
Open access
We report the first evidence for the decay {Sigma}{sup +} {yields} p{mu}{sup +}{mu}{sup -} from data taken by the HyperCP (E871) experiment at Fermilab. Based on three observed events, the branching ...ratio is {Beta}({Sigma}{sup +} {yields} p{mu}{sup +}{mu}{sup -}) = 8.6{sub -5.4}{sup +6.6}(stat) {+-} 5.5(syst) x 10{sup -8}. The narrow range of dimuon masses may indicate that the decay proceeds via a neutral intermediate state, {Sigma}{sup +} {yields} pP{sup 0},P{sup 0} {yields} {mu}{sup +}{mu}{sup -} with a P{sup 0} mass of 214.3 {+-} 0.5 MeV/c{sup 2} and branching ratio {Beta}({Sigma}{sup +} {yields} pP{sup 0}, P{sup 0} {yields} {mu}{sup +}{mu}{sup -}) = 3.1{sub -1.9}{sup +2.4}(stat) {+-} 1.5(syst) x 10{sup -8}.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
The use of accelerated beams of electrons, protons or ions has furthered the development of nearly every scientific discipline. However, high-energy muon beams of equivalent quality have not yet been ...delivered. Muon beams can be created through the decay of pions produced by the interaction of a proton beam with a target. Such 'tertiary' beams have much lower brightness than those created by accelerating electrons, protons or ions. High-brightness muon beams comparable to those produced by state-of-the-art electron, proton and ion accelerators could facilitate the study of lepton-antilepton collisions at extremely high energies and provide well characterized neutrino beams
. Such muon beams could be realized using ionization cooling, which has been proposed to increase muon-beam brightness
. Here we report the realization of ionization cooling, which was confirmed by the observation of an increased number of low-amplitude muons after passage of the muon beam through an absorber, as well as an increase in the corresponding phase-space density. The simulated performance of the ionization cooling system is consistent with the measured data, validating designs of the ionization cooling channel in which the cooling process is repeated to produce a substantial cooling effect
. The results presented here are an important step towards achieving the muon-beam quality required to search for phenomena at energy scales beyond the reach of the Large Hadron Collider at a facility of equivalent or reduced footprint
.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Available symptomatic therapies for the treatment of Alzheimer's disease (AD) have been based on known neurotransmitter dysfunctions associated with the illness. The second-generation cholinesterase ...inhibitors and the N-methyl D-aspartate receptor antagonist memantine have been widely prescribed and studied. Meta-analyses of these therapies were reviewed, focusing on effectiveness and tolerability. Although many of the meta-analyses demonstrate statistically significant improvements, some question if these benefits are sufficient to justify their current widespread and protracted use. This has spurred the development of new disease-modifying therapies that aim to have a greater impact on this debilitating illness.
Muon beams of low emittance provide the basis for the intense, well-characterized neutrino beams necessary to elucidate the physics of flavor at a neutrino factory and to provide lepton-antilepton ...collisions at energies of up to several TeV at a muon collider. The international Muon Ionization Cooling Experiment (MICE) aims to demonstrate ionization cooling, the technique by which it is proposed to reduce the phase-space volume occupied by the muon beam at such facilities. In an ionization-cooling channel, the muon beam passes through a material in which it loses energy. The energy lost is then replaced using rf cavities. The combined effect of energy loss and reacceleration is to reduce the transverse emittance of the beam (transverse cooling). A major revision of the scope of the project was carried out over the summer of 2014. The revised experiment can deliver a demonstration of ionization cooling. The design of the cooling demonstration experiment will be described together with its predicted cooling performance.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM, UPUK
We have compared the p and p angular distributions in 117 x 10(6) Xi- -->Lambdapi- -->ppi-pi- and 41 x 10(6) Xi+ -->Lambda pi+ -->p pi+pi+ decays using a subset of the data from the HyperCP ...experiment (E871) at Fermilab. We find no evidence of CP violation, with the direct-CP-violating parameter AXiLambda identical with (alphaXialphaLambda-alpha Xialpha Lambda)/(alphaXialphaLambda+alphaXialphaLambda)=0.0+/-5.1(stat)+/-4.4(syst) x 10(-4).
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Posttraumatic brain injury patients with depressive symptoms were compared with nondepressed mild and moderate traumatic brain injury (TBI) patients based on their scores on the Rivermead ...Post-Concussion Symptoms Questionnaire (RPCSQ). A factor analysis demonstrated that the items of the RPCSQ loaded into three factors: mood and cognition, general somatic, and visual somatic symptom groups. Factor scores based on this model were calculated for each group and it was found that depressed subjects reported a greater severity of all three symptom groups compared to nondepressed patients. These results suggest that depression post-TBI may influence patient perception of postconcussion symptoms.
Objectives: To determine which serotonergic system-related single nucleotide polymorphisms (SNPs) predicted variation in treatment response to citalopram in depression following a traumatic brain ...injury (TBI).
Methods: Ninety (50 M/40 F, aged 39.9, SD = 18.0 years) post-TBI patients with a major depressive episode (MDE) were recruited into a 6-week open-label study of citalopram (20 mg/day). Six functional SNPs in genes related to the serotonergic system were examined: serotonin transporter (5HTTLPR including rs25531), 5HT1A C-(1019)G and 5HT2A T-(102)C, methylene tetrahydrofolate reductase (MTHFR) C-(677)T, brain-derived neurotrophic factor (BDNF) val66met and tryptophan hydroxylase-2 (TPH2) G-(703)T. Regression analyses were performed using the six SNPs as independent variables: Model 1 with response (percentage Hamilton Depression (HAMD) change from baseline to endpoint) as the dependent variable and Model 2 with adverse event index as the dependent variable (Bonferroni corrected p-value < 0.025).
Results: MTHFR and BDNF SNPs predicted greater treatment response (R2= 0.098, F = 4.65, p = 0.013). The 5HTTLPR predicted greater occurrence of adverse events (R2= 0.069, F = 5.72, p = 0.020).
Conclusion: Results suggest that polymorphisms in genes related to the serotonergic system may help predict short-term response to citalopram and tolerability to the medication in patients with MDE following a TBI.
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